Re-expression
of a developmentally restricted potassium channel in autoimmune
demyelination: Kv1.4 is implicated in oligodendroglial proliferation.

Abstract

Mechanisms
of lesion repair in multiple sclerosis are incompletely understood. To
some degree, remyelination can occur, associated with an increase of
proliferating oligodendroglial cells. Recently, the expression of
potassium channels has been implicated in the control of oligodendrocyte
precursor cell proliferation in vitro. We investigated the expression
of Kv1.4 potassium channels in myelin oligodendrocyte
glycoprotein-induced experimental autoimmune encephalomyelitis, a model
of multiple sclerosis. Confocal microscopy revealed expression of Kv1.4
in AN2-positive oligodendrocyte precursor cells and premyelinating
oligodendrocytes in vitro but neither in mature oligodendrocytes nor in
the spinal cords of healthy adult mice. After induction of myelin
oligodendrocyte glycoprotein-induced experimental autoimmune
encephalomyelitis, Kv1.4 immunoreactivity was detected in or around
lesions already during disease onset with a peak early and a subsequent
decrease in the late phase of the disease. Kv1.4 expression was confined
to 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive
oligodendroglial cells, which were actively proliferating and ensheathed
naked axons. After a demyelinating episode, the number of Kv1.4 and
2',3'-cyclic nucleotide 3'-phosphodiesterase double-positive cells was
greatly reduced in ciliary neurotrophic factor knockout mice, a model
with impaired lesion repair. In summary, the re-expression of an
oligodendroglial potassium channel may have a functional implication on
oligodendroglial cell cycle progression, thus influencing tissue repair
in experimental autoimmune encephalomyelitis and multiple sclerosis.